ArticlePLoS pathogens2022
Lipopolysaccharide -mediated resistance to host antimicrobial peptides and hemocyte-derived reactive-oxygen species are the major Providencia alcalifaciens virulence factors in Drosophila melanogaster.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 32 citations in OpenAlex.
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- Sex bias in iron sequestration by transferrin 1 modulates sexually dimorphic infection outcomes in Drosophila melanogaster.Genetics · 2026Article
- Identification of a novel SXT/R391 integrative and conjugative element harboringFrontiers in microbiology · 2026Article
- Multidrug-Resistant Providencia rettgeri: An Emerging Pathogen in Farmed Siamese Crocodiles (Crocodylus siamensis) in Hainan, China.Transboundary and emerging diseases · 2026Article
- Review
- A comprehensive analysis of the defense responses of Odontotermes formosanus (Shiraki) provides insights into the changes during Serratia marcescens infection.BMC genomics · 2024Article
- Salvianolic acids modulate lifespan and gut microbiota composition in amyloid-β-expressing Drosophila melanogaster.World journal of microbiology & biotechnology · 2024Article
- Pathogenic diversification of the gut commensalInfection and immunity · 2024Article
- The endosymbiontmBio · 2024Article
- Engineered fungus containing a caterpillar gene kills insects rapidly by disrupting their ecto- and endo-microbiomes.Communications biology · 2024Article
- MprF-mediated immune evasion is necessary for Lactiplantibacillus plantarum resilience in the Drosophila gut during inflammation.PLoS pathogens · 2024Article
- When the microbiome shapes the host: immune evolution implications for infectious disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- The Drosophila melanogaster prophenoloxidase system participates in immunity against Zika virus infection.European journal of immunology · 2023Article
- Delayed host mortality and immune response upon infection withInfection and immunity · 2023Article
- Resistance to host antimicrobial peptides mediates resilience of gut commensals during infection and aging inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila.International journal of molecular sciences · 2023Article
- HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection.BMC biology · 2022Article
- Antimicrobial Peptides-Mechanisms of Action, Antimicrobial Effects and Clinical Applications.Antibiotics (Basel, Switzerland) · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Bacteria from the genus Providencia are ubiquitous Gram-negative opportunistic pathogens, causing "travelers' diarrhea", urinary tract, and other nosocomial infections in humans. Some Providencia strains have also been isolated as natural pathogens of Drosophila melanogaster. Despite clinical relevance and extensive use in Drosophila immunity research, little is known about Providencia virulence mechanisms and the corresponding insect host defenses. To close this knowledge gap, we investigated the virulence factors of a representative Providencia species-P. alcalifaciens which is highly virulent to fruit flies and amenable to genetic manipulations. We generated a P. alcalifaciens transposon mutant library and performed an unbiased forward genetics screen in vivo for attenuated mutants. Our screen uncovered 23 mutants with reduced virulence. The vast majority of them had disrupted genes linked to lipopolysaccharide (LPS) synthesis or modifications. These LPS mutants were sensitive to cationic antimicrobial peptides (AMPs) in vitro and their virulence was restored in Drosophila mutants lacking most AMPs. Thus, LPS-mediated resistance to host AMPs is one of the virulence strategies of P. alcalifaciens. Another subset of P. alcalifaciens attenuated mutants exhibited increased susceptibility to reactive oxygen species (ROS) in vitro and their virulence was rescued by chemical scavenging of ROS in flies prior to infection. Using genetic analysis, we found that the enzyme Duox specifically in hemocytes is the source of bactericidal ROS targeting P. alcalifaciens. Consistently, the virulence of ROS-sensitive P. alcalifaciens mutants was rescued in flies with Duox knockdown in hemocytes. Therefore, these genes function as virulence factors by helping bacteria to counteract the ROS immune response. Our reciprocal analysis of host-pathogen interactions between D. melanogaster and P. alcalifaciens identified that AMPs and hemocyte-derived ROS are the major defense mechanisms against P. alcalifaciens, while the ability of the pathogen to resist these host immune responses is its major virulence mechanism. Thus, our work revealed a host-pathogen conflict mediated by ROS and AMPs.
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